Class II antigens are membrane bound glycoproteins that are encoded by genes in the mixed histocompatibility complex (MHC). The expression of these antigens allows a cell to participate in the initiation and perpetuation of immune responses. Furthermore, although most cells that constitutively express class II antigens are members of the immune system, other cell types can be induced to demonstrate these molecules under selected conditions, such as an immunologic or degenerative event. Early investigations demonstrated that patients with the retinal degenerative disorder retinitis pigmentosa had a unique alteration in two regulatory proteins, interferon-gamma and the MHC class II antigen, HLA-DR. In addition, in vitro studies revealed that a regulatory cell in the eye, the rpe cell, could also express this antigen and that these determinants were sensitive to modulation with interferon-gamma. Based on these findings we expanded our studies to evaluate class II antigen expression in ocular diseases. We found that the rpe cell does not express class II antigen in the normal eye. In contrast, the rpe cell did express these molecules in a retinal degenerative disorder (retinitis pigmentosa) and in two ocular inflammatory diseases (sympathetic opthalmia and uveitis). Using the EAU animal model of ocular autoimmune disease we demonstrated that the rpe cell is activated to express class II antigens prior to clinical and histopathological evidence of the disease. We are now evaluating the effects of such modulators as interferon-gamma, anti-Ia antiserum and cyclosporine on class II antigen expression with the hope that an alteration in activation or expression of these molecules may modify the disease process to the benefit of the host. In summary, these studies indicate that the appearance and modulation of class II antigens may play a role in the initiation, maintenance or regulation of pathologic events in degenerative or inflammatory processes.